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Q13686 (ALKB1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 112. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Alkylated DNA repair protein alkB homolog 1

EC=1.14.11.33
Alternative name(s):
Alpha-ketoglutarate-dependent dioxygenase ABH1
DNA lyase ABH1
EC=4.2.99.18
DNA oxidative demethylase ALKBH1
Gene names
Name:ALKBH1
Synonyms:ABH, ABH1, ALKBH
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length389 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Dioxygenase that repairs alkylated single-stranded DNA and RNA containing 3-methylcytosine by oxidative demethylation. Requires molecular oxygen, alpha-ketoglutarate and iron. May have a role in placental trophoblast lineage differentiation By similarity. Has DNA lyase activity and introduces double-stranded breaks at abasic sites. Cleaves both single-stranded DNA and double-stranded DNA at abasic sites, with the greatest activity towards double-stranded DNA with two abasic sites. DNA lyase activity does not require alpha-ketoglutarate and iron. Ref.5 Ref.6

Catalytic activity

The C-O-P bond 3' to the apurinic or apyrimidinic site in DNA is broken by a beta-elimination reaction, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate.

DNA-base-CH3 + 2-oxoglutarate + O2 = DNA-base + formaldehyde + succinate + CO2.

Cofactor

Binds 1 Fe2+ ion per subunit. Ref.5

Subunit structure

Monomer. Interacts with DNAJB6 By similarity. Ref.6

Subcellular location

Mitochondrion. Nucleus By similarity. Note: Mainly localizes in euchromatin, largely excluded from heterochromatin and nucleoli By similarity. Ref.4 Ref.5

Tissue specificity

Ubiquitous. Ref.4 Ref.5

Sequence similarities

Belongs to the alkB family.

Contains 1 Fe2OG dioxygenase domain.

Caution

Detected in cytoplasm and nucleus When expressed as fusion protein with an N-terminal tag, or when the first 26 N-terminal residues are removed (Ref.4 and Ref.5). The endogenous, unmodified protein localizes to mitochondria (Ref.5).

Sequence caution

The sequence CAA63047.1 differs from that shown. Reason: Frameshift at several positions.

Ontologies

Keywords
   Biological processDNA damage
DNA repair
RNA repair
   Cellular componentMitochondrion
Nucleus
   Coding sequence diversityPolymorphism
   LigandIron
Metal-binding
   Molecular functionDioxygenase
Lyase
Oxidoreductase
   Technical termComplete proteome
Multifunctional enzyme
Reference proteome
Gene Ontology (GO)
   Biological_processDNA catabolic process, endonucleolytic

Inferred from direct assay Ref.6. Source: GOC

DNA dealkylation involved in DNA repair

Inferred from direct assay Ref.5. Source: UniProtKB

DNA demethylation

Inferred from direct assay Ref.5. Source: UniProtKB

DNA repair

Inferred from direct assay Ref.5Ref.6. Source: UniProtKB

RNA repair

Inferred from direct assay Ref.5. Source: UniProtKB

developmental growth

Inferred from electronic annotation. Source: Ensembl

in utero embryonic development

Inferred from electronic annotation. Source: Ensembl

negative regulation of neuron apoptotic process

Inferred from electronic annotation. Source: Ensembl

neuron migration

Inferred from electronic annotation. Source: Ensembl

neuron projection development

Inferred from electronic annotation. Source: Ensembl

oxidative demethylation

Inferred from direct assay Ref.5. Source: UniProtKB

placenta development

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentmitochondrion

Inferred from direct assay Ref.5. Source: UniProtKB

nuclear euchromatin

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionDNA-(apurinic or apyrimidinic site) lyase activity

Inferred from direct assay Ref.6. Source: UniProtKB

chemoattractant activity

Inferred from electronic annotation. Source: Ensembl

ferrous iron binding

Inferred from direct assay Ref.5. Source: UniProtKB

methylcytosine dioxygenase activity

Inferred from direct assay Ref.5. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 389389Alkylated DNA repair protein alkB homolog 1
PRO_0000066668

Regions

Domain208 – 347140Fe2OG dioxygenase
Region177 – 1793Substrate binding By similarity
Region220 – 2223Alpha-ketoglutarate binding By similarity
Region338 – 3447Alpha-ketoglutarate binding By similarity

Sites

Metal binding2311Iron; catalytic By similarity
Metal binding2331Iron; catalytic By similarity
Metal binding2871Iron; catalytic By similarity
Binding site1701Substrate By similarity
Binding site2611Substrate By similarity

Natural variations

Natural variant1351M → I.
Corresponds to variant rs17825440 [ dbSNP | Ensembl ].
VAR_048221
Natural variant3241M → L.
Corresponds to variant rs6494 [ dbSNP | Ensembl ].
VAR_048222

Experimental info

Mutagenesis2181I → L: Reduces Fe2OG dioxygenase activity by 50%. Ref.5
Mutagenesis2311H → A: Near loss of Fe2OG dioxygenase activity. No effect on DNA lyase activity. Ref.5 Ref.6
Mutagenesis2331D → A: Loss of Fe2OG dioxygenase activity. No effect on DNA lyase activity. Ref.5 Ref.6
Mutagenesis2871H → A: Loss of Fe2OG dioxygenase activity. No effect on DNA lyase activity. Ref.5 Ref.6
Mutagenesis3381R → A: Reduced Fe2OG dioxygenase activity. Ref.5
Mutagenesis3441R → A: Reduced Fe2OG dioxygenase activity. Ref.5
Sequence conflict1331K → T in CAA63047. Ref.1
Sequence conflict266 – 2672TA → PP in CAA63047. Ref.1
Sequence conflict3881D → H in AAH25787. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Q13686 [UniParc].

Last modified December 1, 2000. Version 2.
Checksum: 539C4CE41D2D8AEC

FASTA38943,832
        10         20         30         40         50         60 
MGKMAAAVGS VATLATEPGE DAFRKLFRFY RQSRPGTADL EGVIDFSAAH AARGKGPGAQ 

        70         80         90        100        110        120 
KVIKSQLNVS SVSEQNAYRA GLQPVSKWQA YGLKGYPGFI FIPNPFLPGY QWHWVKQCLK 

       130        140        150        160        170        180 
LYSQKPNVCN LDKHMSKEET QDLWEQSKEF LRYKEATKRR PRSLLEKLRW VTVGYHYNWD 

       190        200        210        220        230        240 
SKKYSADHYT PFPSDLGFLS EQVAAACGFE DFRAEAGILN YYRLDSTLGI HVDRSELDHS 

       250        260        270        280        290        300 
KPLLSFSFGQ SAIFLLGGLQ RDEAPTAMFM HSGDIMIMSG FSRLLNHAVP RVLPNPEGEG 

       310        320        330        340        350        360 
LPHCLEAPLP AVLPRDSMVE PCSMEDWQVC ASYLKTARVN MTVRQVLATD QNFPLEPIED 

       370        380 
EKRDISTEGF CHLDDQNSEV KRARINPDS 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning and functional analysis of a human cDNA encoding an Escherichia coli AlkB homolog, a protein involved in DNA alkylation damage repair."
Wei Y.F., Carter K.C., Wang R.P., Shell B.K.
Nucleic Acids Res. 24:931-937(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Synovial sarcoma.
[2]"The DNA sequence and analysis of human chromosome 14."
Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. expand/collapse author list , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J.
Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Pancreas.
[4]"Expression and sub-cellular localization of human ABH family molecules."
Tsujikawa K., Koike K., Kitae K., Shinkawa A., Arima H., Suzuki T., Tsuchiya M., Makino Y., Furukawa T., Konishi N., Yamamoto H.
J. Cell. Mol. Med. 11:1105-1116(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[5]"Human AlkB homolog 1 is a mitochondrial protein that demethylates 3-methylcytosine in DNA and RNA."
Westbye M.P., Feyzi E., Aas P.A., Vagbo C.B., Talstad V.A., Kavli B., Hagen L., Sundheim O., Akbari M., Liabakk N.B., Slupphaug G., Otterlei M., Krokan H.E.
J. Biol. Chem. 283:25046-25056(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, COFACTOR, SUBCELLULAR LOCATION, MUTAGENESIS OF ILE-218; HIS-231; ASP-233; HIS-287; ARG-338 AND ARG-344, IDENTIFICATION BY MASS SPECTROMETRY, TISSUE SPECIFICITY.
[6]"Human AlkB homologue 1 (ABH1) exhibits DNA lyase activity at abasic sites."
Muller T.A., Meek K., Hausinger R.P.
DNA Repair 9:58-65(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF HIS-231; ASP-233 AND HIS-287, SUBUNIT.
[7]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X91992 mRNA. Translation: CAA63047.1. Frameshift.
AC008044 Genomic DNA. Translation: AAF01478.1.
BC025787 mRNA. Translation: AAH25787.1.
PIRS64736.
RefSeqNP_006011.2. NM_006020.2.
UniGeneHs.94542.

3D structure databases

ProteinModelPortalQ13686.
SMRQ13686. Positions 189-289.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114372. 2 interactions.
STRING9606.ENSP00000216489.

PTM databases

PhosphoSiteQ13686.

Proteomic databases

PaxDbQ13686.
PRIDEQ13686.

Protocols and materials databases

DNASU8846.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000216489; ENSP00000216489; ENSG00000100601.
GeneID8846.
KEGGhsa:8846.
UCSCuc001xuc.1. human.

Organism-specific databases

CTD8846.
GeneCardsGC14M078138.
H-InvDBHIX0011855.
HGNCHGNC:17911. ALKBH1.
HPAHPA044087.
MIM605345. gene.
neXtProtNX_Q13686.
PharmGKBPA134906996.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG3145.
HOGENOMHOG000033905.
HOVERGENHBG050487.
InParanoidQ13686.
KOK10765.
OMAKKYSADH.
OrthoDBEOG71P2CK.
PhylomeDBQ13686.
TreeFamTF314609.

Gene expression databases

ArrayExpressQ13686.
BgeeQ13686.
CleanExHS_ALKBH1.
GenevestigatorQ13686.

Family and domain databases

Gene3D2.60.120.590. 2 hits.
InterProIPR004574. Alkb.
IPR027450. AlkB-like.
IPR005123. Oxoglu/Fe-dep_dioxygenase.
[Graphical view]
PfamPF13532. 2OG-FeII_Oxy_2. 1 hit.
[Graphical view]
TIGRFAMsTIGR00568. alkb. 1 hit.
PROSITEPS51471. FE2OG_OXY. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi8846.
NextBio33208.
PROQ13686.
SOURCESearch...

Entry information

Entry nameALKB1_HUMAN
AccessionPrimary (citable) accession number: Q13686
Secondary accession number(s): Q8TAU1, Q9ULA7
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: December 1, 2000
Last modified: April 16, 2014
This is version 112 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM